The Genetic Landscape of Renal Complications in Type 1 Diabetes.
Identifieur interne : 000268 ( PubMed/Checkpoint ); précédent : 000267; suivant : 000269The Genetic Landscape of Renal Complications in Type 1 Diabetes.
Auteurs : Niina Sandholm [Finlande] ; Natalie Van Zuydam ; Emma Ahlqvist [Suède] ; Thorhildur Juliusdottir ; Harshal A. Deshmukh [Royaume-Uni] ; N William Rayner ; Barbara Di Camillo [Italie] ; Carol Forsblom [Finlande] ; Joao Fadista [Suède] ; Daniel Ziemek [Allemagne] ; Rany M. Salem ; Linda T. Hiraki [Canada] ; Marcus Pezzolesi [États-Unis] ; David Trégouët [France] ; Emma Dahlström [Finlande] ; Erkka Valo [Finlande] ; Nikolay Oskolkov [Suède] ; Claes Ladenvall [Suède] ; M Loredana Marcovecchio ; Jason Cooper [Royaume-Uni] ; Francesco Sambo [Italie] ; Alberto Malovini [Italie] ; Marco Manfrini [Italie] ; Amy Jayne Mcknight [Royaume-Uni] ; Maria Lajer [Danemark] ; Valma Harjutsalo [Finlande] ; Daniel Gordin [Finlande] ; Maija Parkkonen [Finlande] ; Valeriya Lyssenko [Suède] ; Paul M. Mckeigue [Royaume-Uni] ; Stephen S. Rich [États-Unis] ; Mary Julia Brosnan ; Eric Fauman [États-Unis] ; Riccardo Bellazzi [Italie] ; Peter Rossing [Danemark] ; Samy Hadjadj [France] ; Andrzej Krolewski [États-Unis] ; Andrew D. Paterson [Canada] ; Joel N. Hirschhorn ; Alexander P. Maxwell [Royaume-Uni] ; Claudio Cobelli [Italie] ; Helen M. Colhoun [Royaume-Uni] ; Leif Groop [Suède] ; Mark I. Mccarthy ; Per-Henrik Groop [Finlande]Source :
- Journal of the American Society of Nephrology : JASN [ 1533-3450 ] ; 2017.
Descripteurs français
- KwdFr :
- MESH :
English descriptors
- KwdEn :
- MESH :
- complications : Diabetes Mellitus, Type 1.
- genetics : Diabetes Mellitus, Type 1, Diabetic Nephropathies.
- Adolescent, Adult, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Young Adult.
Abstract
Diabetes is the leading cause of ESRD. Despite evidence for a substantial heritability of diabetic kidney disease, efforts to identify genetic susceptibility variants have had limited success. We extended previous efforts in three dimensions, examining a more comprehensive set of genetic variants in larger numbers of subjects with type 1 diabetes characterized for a wider range of cross-sectional diabetic kidney disease phenotypes. In 2843 subjects, we estimated that the heritability of diabetic kidney disease was 35% (P=6.4×10(-3)). Genome-wide association analysis and replication in 12,540 individuals identified no single variants reaching stringent levels of significance and, despite excellent power, provided little independent confirmation of previously published associated variants. Whole-exome sequencing in 997 subjects failed to identify any large-effect coding alleles of lower frequency influencing the risk of diabetic kidney disease. However, sets of alleles increasing body mass index (P=2.2×10(-5)) and the risk of type 2 diabetes (P=6.1×10(-4)) associated with the risk of diabetic kidney disease. We also found genome-wide genetic correlation between diabetic kidney disease and failure at smoking cessation (P=1.1×10(-4)). Pathway analysis implicated ascorbate and aldarate metabolism (P=9.0×10(-6)), and pentose and glucuronate interconversions (P=3.0×10(-6)) in pathogenesis of diabetic kidney disease. These data provide further evidence for the role of genetic factors influencing diabetic kidney disease in those with type 1 diabetes and highlight some key pathways that may be responsible. Altogether these results reveal important biology behind the major cause of kidney disease.
DOI: 10.1681/ASN.2016020231
PubMed: 27647854
Affiliations:
- Allemagne, Canada, Danemark, Finlande, France, Italie, Royaume-Uni, Suède, États-Unis
- Angleterre, Angleterre de l'Est, Berlin, Massachusetts, Nouvelle-Aquitaine, Poitou-Charentes, Virginie, Écosse, Île-de-France
- Berlin, Cambridge, Paris, Poitiers, Édimbourg
- Université d'Édimbourg, Université de Cambridge
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pubmed:27647854Le document en format XML
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<author><name sortKey="Lajer, Maria" sort="Lajer, Maria" uniqKey="Lajer M" first="Maria" last="Lajer">Maria Lajer</name>
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<author><name sortKey="Harjutsalo, Valma" sort="Harjutsalo, Valma" uniqKey="Harjutsalo V" first="Valma" last="Harjutsalo">Valma Harjutsalo</name>
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<author><name sortKey="Gordin, Daniel" sort="Gordin, Daniel" uniqKey="Gordin D" first="Daniel" last="Gordin">Daniel Gordin</name>
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<author><name sortKey="Parkkonen, Maija" sort="Parkkonen, Maija" uniqKey="Parkkonen M" first="Maija" last="Parkkonen">Maija Parkkonen</name>
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<author><name sortKey="Lyssenko, Valeriya" sort="Lyssenko, Valeriya" uniqKey="Lyssenko V" first="Valeriya" last="Lyssenko">Valeriya Lyssenko</name>
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<country xml:lang="fr">Suède</country>
<wicri:regionArea>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö</wicri:regionArea>
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<author><name sortKey="Mckeigue, Paul M" sort="Mckeigue, Paul M" uniqKey="Mckeigue P" first="Paul M" last="Mckeigue">Paul M. Mckeigue</name>
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<author><name sortKey="Rich, Stephen S" sort="Rich, Stephen S" uniqKey="Rich S" first="Stephen S" last="Rich">Stephen S. Rich</name>
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</placeName>
<wicri:cityArea>Center for Public Health Genomics, University of Virginia, Charlottesville</wicri:cityArea>
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<author><name sortKey="Brosnan, Mary Julia" sort="Brosnan, Mary Julia" uniqKey="Brosnan M" first="Mary Julia" last="Brosnan">Mary Julia Brosnan</name>
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<author><name sortKey="Fauman, Eric" sort="Fauman, Eric" uniqKey="Fauman E" first="Eric" last="Fauman">Eric Fauman</name>
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<author><name sortKey="Bellazzi, Riccardo" sort="Bellazzi, Riccardo" uniqKey="Bellazzi R" first="Riccardo" last="Bellazzi">Riccardo Bellazzi</name>
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<author><name sortKey="Rossing, Peter" sort="Rossing, Peter" uniqKey="Rossing P" first="Peter" last="Rossing">Peter Rossing</name>
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<author><name sortKey="Hadjadj, Samy" sort="Hadjadj, Samy" uniqKey="Hadjadj S" first="Samy" last="Hadjadj">Samy Hadjadj</name>
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<country xml:lang="fr">France</country>
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<author><name sortKey="Krolewski, Andrzej" sort="Krolewski, Andrzej" uniqKey="Krolewski A" first="Andrzej" last="Krolewski">Andrzej Krolewski</name>
<affiliation wicri:level="2"><nlm:affiliation>Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston, Massachusetts.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston</wicri:cityArea>
</affiliation>
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<author><name sortKey="Paterson, Andrew D" sort="Paterson, Andrew D" uniqKey="Paterson A" first="Andrew D" last="Paterson">Andrew D. Paterson</name>
<affiliation wicri:level="1"><nlm:affiliation>Genetics and Genome Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada.</nlm:affiliation>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Genetics and Genome Biology Program, Hospital for Sick Children, Toronto, Ontario</wicri:regionArea>
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<author><name sortKey="Hirschhorn, Joel N" sort="Hirschhorn, Joel N" uniqKey="Hirschhorn J" first="Joel N" last="Hirschhorn">Joel N. Hirschhorn</name>
<affiliation><nlm:affiliation>Departments of Genetics, and.</nlm:affiliation>
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</affiliation>
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<author><name sortKey="Maxwell, Alexander P" sort="Maxwell, Alexander P" uniqKey="Maxwell A" first="Alexander P" last="Maxwell">Alexander P. Maxwell</name>
<affiliation wicri:level="1"><nlm:affiliation>Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast</wicri:regionArea>
<wicri:noRegion>Belfast</wicri:noRegion>
</affiliation>
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<author><name sortKey="Cobelli, Claudio" sort="Cobelli, Claudio" uniqKey="Cobelli C" first="Claudio" last="Cobelli">Claudio Cobelli</name>
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<affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation>
<country xml:lang="fr">Suède</country>
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</affiliation>
</author>
<author><name sortKey="Mccarthy, Mark I" sort="Mccarthy, Mark I" uniqKey="Mccarthy M" first="Mark I" last="Mccarthy">Mark I. Mccarthy</name>
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<author><name sortKey="Groop, Per Henrik" sort="Groop, Per Henrik" uniqKey="Groop P" first="Per-Henrik" last="Groop">Per-Henrik Groop</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">The Genetic Landscape of Renal Complications in Type 1 Diabetes.</title>
<author><name sortKey="Sandholm, Niina" sort="Sandholm, Niina" uniqKey="Sandholm N" first="Niina" last="Sandholm">Niina Sandholm</name>
<affiliation wicri:level="1"><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</nlm:affiliation>
<country xml:lang="fr">Finlande</country>
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</affiliation>
</author>
<author><name sortKey="Van Zuydam, Natalie" sort="Van Zuydam, Natalie" uniqKey="Van Zuydam N" first="Natalie" last="Van Zuydam">Natalie Van Zuydam</name>
<affiliation><nlm:affiliation>Wellcome Trust Centre for Human Genetics, and.</nlm:affiliation>
<wicri:noCountry code="subField">and</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Ahlqvist, Emma" sort="Ahlqvist, Emma" uniqKey="Ahlqvist E" first="Emma" last="Ahlqvist">Emma Ahlqvist</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö</wicri:regionArea>
<wicri:noRegion>Malmö</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Juliusdottir, Thorhildur" sort="Juliusdottir, Thorhildur" uniqKey="Juliusdottir T" first="Thorhildur" last="Juliusdottir">Thorhildur Juliusdottir</name>
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</affiliation>
</author>
<author><name sortKey="Deshmukh, Harshal A" sort="Deshmukh, Harshal A" uniqKey="Deshmukh H" first="Harshal A" last="Deshmukh">Harshal A. Deshmukh</name>
<affiliation wicri:level="1"><nlm:affiliation>Division of Population Health Sciences, University of Dundee, Dundee, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Division of Population Health Sciences, University of Dundee, Dundee</wicri:regionArea>
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</author>
<author><name sortKey="Rayner, N William" sort="Rayner, N William" uniqKey="Rayner N" first="N William" last="Rayner">N William Rayner</name>
<affiliation><nlm:affiliation>Wellcome Trust Centre for Human Genetics, and.</nlm:affiliation>
<wicri:noCountry code="subField">and</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Di Camillo, Barbara" sort="Di Camillo, Barbara" uniqKey="Di Camillo B" first="Barbara" last="Di Camillo">Barbara Di Camillo</name>
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<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Information Engineering, University of Padova, Padova</wicri:regionArea>
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</author>
<author><name sortKey="Forsblom, Carol" sort="Forsblom, Carol" uniqKey="Forsblom C" first="Carol" last="Forsblom">Carol Forsblom</name>
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<country xml:lang="fr">Finlande</country>
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</author>
<author><name sortKey="Fadista, Joao" sort="Fadista, Joao" uniqKey="Fadista J" first="Joao" last="Fadista">Joao Fadista</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö</wicri:regionArea>
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</author>
<author><name sortKey="Ziemek, Daniel" sort="Ziemek, Daniel" uniqKey="Ziemek D" first="Daniel" last="Ziemek">Daniel Ziemek</name>
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<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Computational Sciences, Pfizer Worldwide Research and Development, Berlin</wicri:regionArea>
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<settlement type="city">Berlin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Salem, Rany M" sort="Salem, Rany M" uniqKey="Salem R" first="Rany M" last="Salem">Rany M. Salem</name>
<affiliation><nlm:affiliation>Departments of Genetics, and.</nlm:affiliation>
<wicri:noCountry code="subField">and</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Hiraki, Linda T" sort="Hiraki, Linda T" uniqKey="Hiraki L" first="Linda T" last="Hiraki">Linda T. Hiraki</name>
<affiliation wicri:level="1"><nlm:affiliation>Genetics and Genome Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada.</nlm:affiliation>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Genetics and Genome Biology Program, Hospital for Sick Children, Toronto, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
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<author><name sortKey="Pezzolesi, Marcus" sort="Pezzolesi, Marcus" uniqKey="Pezzolesi M" first="Marcus" last="Pezzolesi">Marcus Pezzolesi</name>
<affiliation wicri:level="2"><nlm:affiliation>Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston, Massachusetts.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Tregouet, David" sort="Tregouet, David" uniqKey="Tregouet D" first="David" last="Trégouët">David Trégouët</name>
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<country xml:lang="fr">France</country>
<wicri:regionArea>Sorbonne Universities, Pierre et Marie Curie University (UPMC) and National Institute for Health and Medical Research, Mixed Research Unit in Health (UMR_S) 1166, Paris</wicri:regionArea>
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</author>
<author><name sortKey="Dahlstrom, Emma" sort="Dahlstrom, Emma" uniqKey="Dahlstrom E" first="Emma" last="Dahlström">Emma Dahlström</name>
<affiliation wicri:level="1"><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</nlm:affiliation>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki</wicri:regionArea>
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</author>
<author><name sortKey="Valo, Erkka" sort="Valo, Erkka" uniqKey="Valo E" first="Erkka" last="Valo">Erkka Valo</name>
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<country xml:lang="fr">Finlande</country>
<wicri:regionArea>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki</wicri:regionArea>
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</affiliation>
</author>
<author><name sortKey="Oskolkov, Nikolay" sort="Oskolkov, Nikolay" uniqKey="Oskolkov N" first="Nikolay" last="Oskolkov">Nikolay Oskolkov</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö</wicri:regionArea>
<wicri:noRegion>Malmö</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ladenvall, Claes" sort="Ladenvall, Claes" uniqKey="Ladenvall C" first="Claes" last="Ladenvall">Claes Ladenvall</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö</wicri:regionArea>
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</affiliation>
</author>
<author><name sortKey="Marcovecchio, M Loredana" sort="Marcovecchio, M Loredana" uniqKey="Marcovecchio M" first="M Loredana" last="Marcovecchio">M Loredana Marcovecchio</name>
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<wicri:noCountry code="subField">and</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Cooper, Jason" sort="Cooper, Jason" uniqKey="Cooper J" first="Jason" last="Cooper">Jason Cooper</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge</wicri:regionArea>
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<region type="country">Angleterre</region>
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<author><name sortKey="Sambo, Francesco" sort="Sambo, Francesco" uniqKey="Sambo F" first="Francesco" last="Sambo">Francesco Sambo</name>
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<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Information Engineering, University of Padova, Padova</wicri:regionArea>
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</author>
<author><name sortKey="Malovini, Alberto" sort="Malovini, Alberto" uniqKey="Malovini A" first="Alberto" last="Malovini">Alberto Malovini</name>
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<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia</wicri:regionArea>
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</author>
<author><name sortKey="Manfrini, Marco" sort="Manfrini, Marco" uniqKey="Manfrini M" first="Marco" last="Manfrini">Marco Manfrini</name>
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<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Information Engineering, University of Padova, Padova</wicri:regionArea>
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</author>
<author><name sortKey="Mcknight, Amy Jayne" sort="Mcknight, Amy Jayne" uniqKey="Mcknight A" first="Amy Jayne" last="Mcknight">Amy Jayne Mcknight</name>
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<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast</wicri:regionArea>
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</author>
<author><name sortKey="Lajer, Maria" sort="Lajer, Maria" uniqKey="Lajer M" first="Maria" last="Lajer">Maria Lajer</name>
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<country xml:lang="fr">Danemark</country>
<wicri:regionArea>Diabetic Complications, Steno Diabetes Center, Gentofte</wicri:regionArea>
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</author>
<author><name sortKey="Harjutsalo, Valma" sort="Harjutsalo, Valma" uniqKey="Harjutsalo V" first="Valma" last="Harjutsalo">Valma Harjutsalo</name>
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<country xml:lang="fr">Finlande</country>
<wicri:regionArea>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki</wicri:regionArea>
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</affiliation>
</author>
<author><name sortKey="Gordin, Daniel" sort="Gordin, Daniel" uniqKey="Gordin D" first="Daniel" last="Gordin">Daniel Gordin</name>
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<country xml:lang="fr">Finlande</country>
<wicri:regionArea>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki</wicri:regionArea>
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</author>
<author><name sortKey="Parkkonen, Maija" sort="Parkkonen, Maija" uniqKey="Parkkonen M" first="Maija" last="Parkkonen">Maija Parkkonen</name>
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<country xml:lang="fr">Finlande</country>
<wicri:regionArea>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki</wicri:regionArea>
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</affiliation>
</author>
<author><name sortKey="Lyssenko, Valeriya" sort="Lyssenko, Valeriya" uniqKey="Lyssenko V" first="Valeriya" last="Lyssenko">Valeriya Lyssenko</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö</wicri:regionArea>
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</affiliation>
</author>
<author><name sortKey="Mckeigue, Paul M" sort="Mckeigue, Paul M" uniqKey="Mckeigue P" first="Paul M" last="Mckeigue">Paul M. Mckeigue</name>
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<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Centre for Population Health Sciences, University of Edinburgh, Edinburgh</wicri:regionArea>
<placeName><settlement type="city">Édimbourg</settlement>
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<settlement type="city">Édimbourg</settlement>
</placeName>
<orgName type="university">Université d'Édimbourg</orgName>
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</author>
<author><name sortKey="Rich, Stephen S" sort="Rich, Stephen S" uniqKey="Rich S" first="Stephen S" last="Rich">Stephen S. Rich</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Virginie</region>
</placeName>
<wicri:cityArea>Center for Public Health Genomics, University of Virginia, Charlottesville</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Brosnan, Mary Julia" sort="Brosnan, Mary Julia" uniqKey="Brosnan M" first="Mary Julia" last="Brosnan">Mary Julia Brosnan</name>
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</affiliation>
</author>
<author><name sortKey="Fauman, Eric" sort="Fauman, Eric" uniqKey="Fauman E" first="Eric" last="Fauman">Eric Fauman</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Computational Sciences, Pfizer Worldwide Research and Development, Cambridge</wicri:cityArea>
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</author>
<author><name sortKey="Bellazzi, Riccardo" sort="Bellazzi, Riccardo" uniqKey="Bellazzi R" first="Riccardo" last="Bellazzi">Riccardo Bellazzi</name>
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<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia</wicri:regionArea>
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</author>
<author><name sortKey="Rossing, Peter" sort="Rossing, Peter" uniqKey="Rossing P" first="Peter" last="Rossing">Peter Rossing</name>
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<country xml:lang="fr">Danemark</country>
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<author><name sortKey="Hadjadj, Samy" sort="Hadjadj, Samy" uniqKey="Hadjadj S" first="Samy" last="Hadjadj">Samy Hadjadj</name>
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<country xml:lang="fr">France</country>
<wicri:regionArea>Functional Research Unit of Medicine and Pharmacy, University of Poitiers, Poitiers</wicri:regionArea>
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<author><name sortKey="Krolewski, Andrzej" sort="Krolewski, Andrzej" uniqKey="Krolewski A" first="Andrzej" last="Krolewski">Andrzej Krolewski</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
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<author><name sortKey="Paterson, Andrew D" sort="Paterson, Andrew D" uniqKey="Paterson A" first="Andrew D" last="Paterson">Andrew D. Paterson</name>
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<country xml:lang="fr">Canada</country>
<wicri:regionArea>Genetics and Genome Biology Program, Hospital for Sick Children, Toronto, Ontario</wicri:regionArea>
<wicri:noRegion>Ontario</wicri:noRegion>
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</author>
<author><name sortKey="Hirschhorn, Joel N" sort="Hirschhorn, Joel N" uniqKey="Hirschhorn J" first="Joel N" last="Hirschhorn">Joel N. Hirschhorn</name>
<affiliation><nlm:affiliation>Departments of Genetics, and.</nlm:affiliation>
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</affiliation>
</author>
<author><name sortKey="Maxwell, Alexander P" sort="Maxwell, Alexander P" uniqKey="Maxwell A" first="Alexander P" last="Maxwell">Alexander P. Maxwell</name>
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<country xml:lang="fr">Royaume-Uni</country>
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<author><name sortKey="Cobelli, Claudio" sort="Cobelli, Claudio" uniqKey="Cobelli C" first="Claudio" last="Cobelli">Claudio Cobelli</name>
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<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Information Engineering, University of Padova, Padova</wicri:regionArea>
<wicri:noRegion>Padova</wicri:noRegion>
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</author>
<author><name sortKey="Colhoun, Helen M" sort="Colhoun, Helen M" uniqKey="Colhoun H" first="Helen M" last="Colhoun">Helen M. Colhoun</name>
<affiliation wicri:level="1"><nlm:affiliation>Division of Population Health Sciences, University of Dundee, Dundee, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
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<author><name sortKey="Groop, Leif" sort="Groop, Leif" uniqKey="Groop L" first="Leif" last="Groop">Leif Groop</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</nlm:affiliation>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö</wicri:regionArea>
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</affiliation>
</author>
<author><name sortKey="Mccarthy, Mark I" sort="Mccarthy, Mark I" uniqKey="Mccarthy M" first="Mark I" last="Mccarthy">Mark I. Mccarthy</name>
<affiliation><nlm:affiliation>Wellcome Trust Centre for Human Genetics, and.</nlm:affiliation>
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</affiliation>
</author>
<author><name sortKey="Groop, Per Henrik" sort="Groop, Per Henrik" uniqKey="Groop P" first="Per-Henrik" last="Groop">Per-Henrik Groop</name>
<affiliation wicri:level="1"><nlm:affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland; per-henrik.groop@helsinki.fi.</nlm:affiliation>
<country wicri:rule="url">Finlande</country>
<wicri:regionArea>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki</wicri:regionArea>
<wicri:noRegion>Helsinki</wicri:noRegion>
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<series><title level="j">Journal of the American Society of Nephrology : JASN</title>
<idno type="eISSN">1533-3450</idno>
<imprint><date when="2017" type="published">2017</date>
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<term>Adult</term>
<term>Diabetes Mellitus, Type 1 (complications)</term>
<term>Diabetes Mellitus, Type 1 (genetics)</term>
<term>Diabetic Nephropathies (genetics)</term>
<term>Female</term>
<term>Genome-Wide Association Study</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Young Adult</term>
</keywords>
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<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Diabète de type 1 ()</term>
<term>Diabète de type 1 (génétique)</term>
<term>Femelle</term>
<term>Humains</term>
<term>Jeune adulte</term>
<term>Mâle</term>
<term>Néphropathies diabétiques (génétique)</term>
<term>Étude d'association pangénomique</term>
</keywords>
<keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Diabetes Mellitus, Type 1</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Diabetes Mellitus, Type 1</term>
<term>Diabetic Nephropathies</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Diabète de type 1</term>
<term>Néphropathies diabétiques</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adolescent</term>
<term>Adult</term>
<term>Female</term>
<term>Genome-Wide Association Study</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Young Adult</term>
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<keywords scheme="MESH" xml:lang="fr"><term>Adolescent</term>
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Diabète de type 1</term>
<term>Femelle</term>
<term>Humains</term>
<term>Jeune adulte</term>
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<front><div type="abstract" xml:lang="en">Diabetes is the leading cause of ESRD. Despite evidence for a substantial heritability of diabetic kidney disease, efforts to identify genetic susceptibility variants have had limited success. We extended previous efforts in three dimensions, examining a more comprehensive set of genetic variants in larger numbers of subjects with type 1 diabetes characterized for a wider range of cross-sectional diabetic kidney disease phenotypes. In 2843 subjects, we estimated that the heritability of diabetic kidney disease was 35% (P=6.4×10(-3)). Genome-wide association analysis and replication in 12,540 individuals identified no single variants reaching stringent levels of significance and, despite excellent power, provided little independent confirmation of previously published associated variants. Whole-exome sequencing in 997 subjects failed to identify any large-effect coding alleles of lower frequency influencing the risk of diabetic kidney disease. However, sets of alleles increasing body mass index (P=2.2×10(-5)) and the risk of type 2 diabetes (P=6.1×10(-4)) associated with the risk of diabetic kidney disease. We also found genome-wide genetic correlation between diabetic kidney disease and failure at smoking cessation (P=1.1×10(-4)). Pathway analysis implicated ascorbate and aldarate metabolism (P=9.0×10(-6)), and pentose and glucuronate interconversions (P=3.0×10(-6)) in pathogenesis of diabetic kidney disease. These data provide further evidence for the role of genetic factors influencing diabetic kidney disease in those with type 1 diabetes and highlight some key pathways that may be responsible. Altogether these results reveal important biology behind the major cause of kidney disease.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27647854</PMID>
<DateCreated><Year>2016</Year>
<Month>09</Month>
<Day>20</Day>
</DateCreated>
<DateCompleted><Year>2017</Year>
<Month>05</Month>
<Day>24</Day>
</DateCompleted>
<DateRevised><Year>2017</Year>
<Month>11</Month>
<Day>16</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1533-3450</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>28</Volume>
<Issue>2</Issue>
<PubDate><Year>2017</Year>
<Month>Feb</Month>
</PubDate>
</JournalIssue>
<Title>Journal of the American Society of Nephrology : JASN</Title>
<ISOAbbreviation>J. Am. Soc. Nephrol.</ISOAbbreviation>
</Journal>
<ArticleTitle>The Genetic Landscape of Renal Complications in Type 1 Diabetes.</ArticleTitle>
<Pagination><MedlinePgn>557-574</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1681/ASN.2016020231</ELocationID>
<Abstract><AbstractText>Diabetes is the leading cause of ESRD. Despite evidence for a substantial heritability of diabetic kidney disease, efforts to identify genetic susceptibility variants have had limited success. We extended previous efforts in three dimensions, examining a more comprehensive set of genetic variants in larger numbers of subjects with type 1 diabetes characterized for a wider range of cross-sectional diabetic kidney disease phenotypes. In 2843 subjects, we estimated that the heritability of diabetic kidney disease was 35% (P=6.4×10(-3)). Genome-wide association analysis and replication in 12,540 individuals identified no single variants reaching stringent levels of significance and, despite excellent power, provided little independent confirmation of previously published associated variants. Whole-exome sequencing in 997 subjects failed to identify any large-effect coding alleles of lower frequency influencing the risk of diabetic kidney disease. However, sets of alleles increasing body mass index (P=2.2×10(-5)) and the risk of type 2 diabetes (P=6.1×10(-4)) associated with the risk of diabetic kidney disease. We also found genome-wide genetic correlation between diabetic kidney disease and failure at smoking cessation (P=1.1×10(-4)). Pathway analysis implicated ascorbate and aldarate metabolism (P=9.0×10(-6)), and pentose and glucuronate interconversions (P=3.0×10(-6)) in pathogenesis of diabetic kidney disease. These data provide further evidence for the role of genetic factors influencing diabetic kidney disease in those with type 1 diabetes and highlight some key pathways that may be responsible. Altogether these results reveal important biology behind the major cause of kidney disease.</AbstractText>
<CopyrightInformation>Copyright © 2017 by the American Society of Nephrology.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Sandholm</LastName>
<ForeName>Niina</ForeName>
<Initials>N</Initials>
<AffiliationInfo><Affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Van Zuydam</LastName>
<ForeName>Natalie</ForeName>
<Initials>N</Initials>
<AffiliationInfo><Affiliation>Wellcome Trust Centre for Human Genetics, and.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Medical Research Institute, and.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ahlqvist</LastName>
<ForeName>Emma</ForeName>
<Initials>E</Initials>
<AffiliationInfo><Affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Juliusdottir</LastName>
<ForeName>Thorhildur</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>Wellcome Trust Centre for Human Genetics, and.</Affiliation>
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<Author ValidYN="Y"><LastName>Deshmukh</LastName>
<ForeName>Harshal A</ForeName>
<Initials>HA</Initials>
<AffiliationInfo><Affiliation>Division of Population Health Sciences, University of Dundee, Dundee, United Kingdom.</Affiliation>
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<Author ValidYN="Y"><LastName>Rayner</LastName>
<ForeName>N William</ForeName>
<Initials>NW</Initials>
<AffiliationInfo><Affiliation>Wellcome Trust Centre for Human Genetics, and.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Human Genetics, Wellcome Trust Sanger Institute, Hinxton, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Di Camillo</LastName>
<ForeName>Barbara</ForeName>
<Initials>B</Initials>
<AffiliationInfo><Affiliation>Department of Information Engineering, University of Padova, Padova, Italy.</Affiliation>
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<Author ValidYN="Y"><LastName>Forsblom</LastName>
<ForeName>Carol</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Fadista</LastName>
<ForeName>Joao</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ziemek</LastName>
<ForeName>Daniel</ForeName>
<Initials>D</Initials>
<AffiliationInfo><Affiliation>Computational Sciences, Pfizer Worldwide Research and Development, Berlin, Germany.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Salem</LastName>
<ForeName>Rany M</ForeName>
<Initials>RM</Initials>
<AffiliationInfo><Affiliation>Departments of Genetics, and.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Programs in Metabolism and Medical and Population Genetics, Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Divisions of Endocrinology and Genetics, Boston Children's Hospital, Boston, Massachusetts.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hiraki</LastName>
<ForeName>Linda T</ForeName>
<Initials>LT</Initials>
<AffiliationInfo><Affiliation>Genetics and Genome Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada.</Affiliation>
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</Author>
<Author ValidYN="Y"><LastName>Pezzolesi</LastName>
<ForeName>Marcus</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston, Massachusetts.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Trégouët</LastName>
<ForeName>David</ForeName>
<Initials>D</Initials>
<AffiliationInfo><Affiliation>Sorbonne Universities, Pierre et Marie Curie University (UPMC) and National Institute for Health and Medical Research, Mixed Research Unit in Health (UMR_S) 1166, Paris, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Institute for Cardiometabolism and Nutrition, Genomics and pathophysiology of Cardiovascular diseases, Paris, France.</Affiliation>
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<Author ValidYN="Y"><LastName>Dahlström</LastName>
<ForeName>Emma</ForeName>
<Initials>E</Initials>
<AffiliationInfo><Affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Valo</LastName>
<ForeName>Erkka</ForeName>
<Initials>E</Initials>
<AffiliationInfo><Affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Oskolkov</LastName>
<ForeName>Nikolay</ForeName>
<Initials>N</Initials>
<AffiliationInfo><Affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ladenvall</LastName>
<ForeName>Claes</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</Affiliation>
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</Author>
<Author ValidYN="Y"><LastName>Marcovecchio</LastName>
<ForeName>M Loredana</ForeName>
<Initials>ML</Initials>
<AffiliationInfo><Affiliation>Department of Paediatrics, Institute of Metabolic Science, and.</Affiliation>
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</Author>
<Author ValidYN="Y"><LastName>Cooper</LastName>
<ForeName>Jason</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom.</Affiliation>
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</Author>
<Author ValidYN="Y"><LastName>Sambo</LastName>
<ForeName>Francesco</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>Department of Information Engineering, University of Padova, Padova, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Malovini</LastName>
<ForeName>Alberto</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Laboratory of Informatics and Systems Engineering for Clinical Research, Scientific Institute for Research, Hospitalization and Health Care, IRCCS (Instituto di Ricovero e Cura a Carattere Scientifico); Salvatore Maugeri Foundation, Pavia, Italy.</Affiliation>
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</Author>
<Author ValidYN="Y"><LastName>Manfrini</LastName>
<ForeName>Marco</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Department of Information Engineering, University of Padova, Padova, Italy.</Affiliation>
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</Author>
<Author ValidYN="Y"><LastName>McKnight</LastName>
<ForeName>Amy Jayne</ForeName>
<Initials>AJ</Initials>
<AffiliationInfo><Affiliation>Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast, United Kingdom.</Affiliation>
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</Author>
<Author ValidYN="Y"><LastName>Lajer</LastName>
<ForeName>Maria</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Diabetic Complications, Steno Diabetes Center, Gentofte, Denmark.</Affiliation>
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<Author ValidYN="Y"><LastName>Harjutsalo</LastName>
<ForeName>Valma</ForeName>
<Initials>V</Initials>
<AffiliationInfo><Affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>The Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gordin</LastName>
<ForeName>Daniel</ForeName>
<Initials>D</Initials>
<AffiliationInfo><Affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Parkkonen</LastName>
<ForeName>Maija</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><CollectiveName>FinnDiane Study Group, Jaakko Tuomilehto</CollectiveName>
</Author>
<Author ValidYN="Y"><LastName>Lyssenko</LastName>
<ForeName>Valeriya</ForeName>
<Initials>V</Initials>
<AffiliationInfo><Affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Diabetic Complications, Steno Diabetes Center, Gentofte, Denmark.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>McKeigue</LastName>
<ForeName>Paul M</ForeName>
<Initials>PM</Initials>
<AffiliationInfo><Affiliation>Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom.</Affiliation>
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</Author>
<Author ValidYN="Y"><LastName>Rich</LastName>
<ForeName>Stephen S</ForeName>
<Initials>SS</Initials>
<AffiliationInfo><Affiliation>Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia.</Affiliation>
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</Author>
<Author ValidYN="Y"><LastName>Brosnan</LastName>
<ForeName>Mary Julia</ForeName>
<Initials>MJ</Initials>
<AffiliationInfo><Affiliation>Cardiovascular and Metabolic Diseases Research Unit, and.</Affiliation>
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</Author>
<Author ValidYN="Y"><LastName>Fauman</LastName>
<ForeName>Eric</ForeName>
<Initials>E</Initials>
<AffiliationInfo><Affiliation>Computational Sciences, Pfizer Worldwide Research and Development, Cambridge, Massachusetts.</Affiliation>
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<Author ValidYN="Y"><LastName>Bellazzi</LastName>
<ForeName>Riccardo</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy.</Affiliation>
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</Author>
<Author ValidYN="Y"><LastName>Rossing</LastName>
<ForeName>Peter</ForeName>
<Initials>P</Initials>
<AffiliationInfo><Affiliation>Diabetic Complications, Steno Diabetes Center, Gentofte, Denmark.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Health, Aarhus University, Aarhus, Denmark.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hadjadj</LastName>
<ForeName>Samy</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Functional Research Unit of Medicine and Pharmacy, University of Poitiers, Poitiers, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Endocrinology-Diabetology and Center of Clinical Investigation, Poitiers University Hospital, Poitiers, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Institute National pour la Santé et la Recherche Médicale, National Institute for Health and Medical Research, Center of Clinical Investigation 1402 and Unit 1082, Poitiers, France.</Affiliation>
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</Author>
<Author ValidYN="Y"><LastName>Krolewski</LastName>
<ForeName>Andrzej</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston, Massachusetts.</Affiliation>
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</Author>
<Author ValidYN="Y"><LastName>Paterson</LastName>
<ForeName>Andrew D</ForeName>
<Initials>AD</Initials>
<AffiliationInfo><Affiliation>Genetics and Genome Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><CollectiveName>DCCT/EDIC Study Group, Jose C. Florez</CollectiveName>
</Author>
<Author ValidYN="Y"><LastName>Hirschhorn</LastName>
<ForeName>Joel N</ForeName>
<Initials>JN</Initials>
<AffiliationInfo><Affiliation>Departments of Genetics, and.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Programs in Metabolism and Medical and Population Genetics, Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Divisions of Endocrinology and Genetics, Boston Children's Hospital, Boston, Massachusetts.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Maxwell</LastName>
<ForeName>Alexander P</ForeName>
<Initials>AP</Initials>
<AffiliationInfo><Affiliation>Nephrology Research, Centre for Public Health, Queen's University of Belfast, Belfast, United Kingdom.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Regional Nephrology Unit, Belfast City Hospital, Belfast, United Kingdom; and.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><CollectiveName>GENIE Consortium, David Dunger</CollectiveName>
</Author>
<Author ValidYN="Y"><LastName>Cobelli</LastName>
<ForeName>Claudio</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Department of Information Engineering, University of Padova, Padova, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Colhoun</LastName>
<ForeName>Helen M</ForeName>
<Initials>HM</Initials>
<AffiliationInfo><Affiliation>Division of Population Health Sciences, University of Dundee, Dundee, United Kingdom.</Affiliation>
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</Author>
<Author ValidYN="Y"><LastName>Groop</LastName>
<ForeName>Leif</ForeName>
<Initials>L</Initials>
<AffiliationInfo><Affiliation>Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital, Lund University, Malmö, Sweden.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>McCarthy</LastName>
<ForeName>Mark I</ForeName>
<Initials>MI</Initials>
<AffiliationInfo><Affiliation>Wellcome Trust Centre for Human Genetics, and.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust, Oxford, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Groop</LastName>
<ForeName>Per-Henrik</ForeName>
<Initials>PH</Initials>
<AffiliationInfo><Affiliation>Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland; per-henrik.groop@helsinki.fi.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Baker IDI (International Diabetes Institute) Heart and Diabetes Institute, Melbourne, Victoria, Australia.</Affiliation>
</AffiliationInfo>
</Author>
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<MeshHeadingList><MeshHeading><DescriptorName UI="D000293" MajorTopicYN="N">Adolescent</DescriptorName>
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<MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName>
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<ForeName>A D</ForeName>
<Initials>AD</Initials>
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<ForeName>J C</ForeName>
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<ForeName>J N</ForeName>
<Initials>JN</Initials>
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<ForeName>A P</ForeName>
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<Investigator ValidYN="Y"><LastName>Colhoun</LastName>
<ForeName>H M</ForeName>
<Initials>HM</Initials>
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<Investigator ValidYN="Y"><LastName>Groop</LastName>
<ForeName>L</ForeName>
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<ForeName>M I</ForeName>
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<Day>26</Day>
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<PubMedPubDate PubStatus="accepted"><Year>2016</Year>
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<Day>17</Day>
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